LH is released from the pituitary gland in pulses of high biological activity. This episodic mode of secretion may obviate gonadotropin-induced desensitization of gonadal cells under hormonal control. The exact nature of glandular secretory events is difficult to discern in vivo, since underlying patterns of hormone release are confounded by metabolic clearance. Using a deconvolution model that allows the calculation of endogenous clearance kinetics and secretory rates simultaneously, multiple parameter deconvolution disclosed endogenous bioactive LH half-life of 53 +/- 5.4 min and an endogenous production rate of 0.48 +/- 0.06 mIU/ml/min. The bioactive LH secretory burst of half duration of 12.2 +/- 1.5 min occurred at intervals of 56 +/- 1.3 min and achieved amplitudes of 2.1 +/- 0.26 mIU min. LH secretory bursts were positively correlated with the duration of the subsequent interpulse interval. Application of the deconvolution algorithm in conjunction with the rat Leydig cell testosterone bioassay revealed the presence of distinct burst-like secretory events acted on by exponential metabolic clearance mechanisms, and provided a good model for analysis of bioactive plasma hormone concentration profiles in vivo. Such multifaceted changes might not be readily apparent using deconvolution techniques requiring known half-lives/or conventional pulse analysis of plasma hormone concentration. The present analysis indicates that endogenous clearance mechanisms provide a mechanism to extend the defined short-lived pituitary secretory events. The multiple parameter deconvolution approach may help to unmask pathophysiological states with alterations in endogenous hormone as well as clearance in vivo. The estrogen time-dependent effects on the kinetics of GnRH's self priming action on the pituitary gland were analyzed in postmenopausal women on intravaginal estradiol replacement. The self-priming action of GnRH on bioactive LH release is maximal after 5 to 10 days of estrogen exposure and can be observed whether it is defined as increase in the percentage amplitude of a second peak of bioactive LH provoked by exogenous GnRH (10 micrograms,i.v) compared to the first LH peak (given at 2-hourly intervals) or as an incremental increase. We conclude that estrogen in the human regulates the pituitary gland's responsiveness to GnRH, such that enhanced secretion of biologically active gonadotropin occurs during serial exposure to GnRH stimulation. The finding of GnRH self-priming induced by estradiol is of importance to an understanding of possible mechanisms governing the generation of the preovulatory gonadotropin surge.